Laboratory methods for monitoring argatroban in heparin‐induced thrombocytopenia

Abstract

Argatroban (Mitsubishi Pharma Europe) is a direct thrombin inhibitor (DTI) currently licensed for anticoagulation of patients with heparininduced thrombocytopenia (HIT), but has been more recently been used in COVID-19 patients and vaccine-induced immune thrombocytopenia and thrombosis (VITT) patients. The Summary of Product Characteristics (SmPC) recommends monitoring using the activated partial thromboplastin time (APTT) ratio with a target of 1.5-3.0 times the initial baseline value; but not exceeding 100 seconds 1 based on the original clinical trial of Swan et al 2 who used the APTT reagent Actin FSL in 73 healthy male volunteers. This is incorporated in the guidelines from British Committee for Standards in Haematology 3 and the American College of Chest Physicians. 4 Lewis et al 5 did a

Effect of direct thrombin inhibitors on laboratory measurement of fibrinogen: Potential for errors in clinical decision‐making

“…Our data are consistent with the 70%-90% underestimation of fibrinogen determined using a low thrombin reagent in the presence of 0.8-1.2 μg/mL argatroban. 14 Studies 7,8 confirm levels of argatroban causing substantial underestimation would be commonly seen during routine use of argatroban therapy.…”

“…The levels in these two samples were consistent with those seen in patients on treatment with argatroban-the mean level of argatroban in patients on standard dosing for HIT was 0.99 μg/mL in one study 7 and 0.84 μg/mL in another. 8 Even when more conservative dosing was used to lower bleeding risk the average argatroban level was 0.6 μg/mL. 8 Two further samples were prepared by pooling citrated plasma from patients receiving argatroban therapy which remained on completion of tests requested for monitoring therapy.…”

“…8 Even when more conservative dosing was used to lower bleeding risk the average argatroban level was 0.6 μg/mL. 8 Two further samples were prepared by pooling citrated plasma from patients receiving argatroban therapy which remained on completion of tests requested for monitoring therapy. Exercise 3-Argatroban: one sample was prepared from a pooled normal plasma, spiked with 0.6 μg/mL argatroban.…”

Thromboprophylaxis with argatroban in critically ill patients with sepsis: a review

“…Whether the aPTT assay is the appropriate tool for monitoring, argatroban treatment is the subject of considerable controversy [204][205][206]. Furthermore, studies indicate that the aPTT does not correlate well with plasma levels in critically ill patients [207,208]. Also, close aPTT monitoring might be challenging in daily ICU routine [209].…”

Use of the CytoSorb® filter for elimination of residual therapeutic argatroban concentrations during heparinized cardiopulmonary bypass for heart transplantation

“…According to institutional standards, monitoring of argatroban was performed using a chromogenic anti-IIa assay (Innovance® DTI assay, Siemens Healthcare, Erlangen, Germany) with a target concentration of 0.4–1.0 μg/ml. 10 After 5 weeks in our hospital, a donor organ was offered. However, due to logistical reasons, the time interval between the offering of the organ and the beginning of surgery was only 2 hours.…”